Background

The aim of this study was to explore changes in mobility in terms of ambulation and transfer over 1 year in patients with early-onset Alzheimer's disease (EOAD), and to compare mobility in EOAD with patients with other types of early-onset dementia (EOOD).

Method

Forty-two patients with EOAD and 30 patients with EOOD were included. All patients were home-dwelling and had mild or moderate degree of dementia. Mobility was assessed using the Timed Up and Go Test (TUG), a modified version of the Clinical Outcome Variables Scale, timed stair walking, and timed rise from the floor.

Results

The EOAD group performed significantly better than the EOOD group on all mobility tests. After 1 year, 25 persons with EOAD were tested again. The performance on TUG (p = 0.028) and stair walking (p = 0.02) had deteriorated at the 1-year follow-up in the EOAD group.

Conclusion

Patients with EOAD performed better on mobility tasks than patients with EOOD, but their performance deteriorated at 1-year follow-up.

Introduction

Autonomic dysfunction is a well-known feature in neurodegenerative dementias, especially common in α-synucleinopathies like dementia with Lewy bodies and Parkinson's disease with dementia. The most common symptoms are orthostatic hypotension, incontinence and constipation, but its relevance in clinical practice is poorly understood. There are no earlier studies addressing the influence of autonomic dysfunction on clinical course and survival. The aim of this study was to investigate the frequency of the three most common features of autonomic dysfunction and analyze how it affects survival.

Methods

Thirty patients with dementia with Lewy bodies and Parkinson's disease with dementia were included in this prospective, longitudinal follow-up study. Presence of incontinence and constipation was recorded at baseline. Blood pressure was measured at baseline, after 3 months and after 6 months according to standardized procedures, with 5 measurements during 10 minutes after rising. Orthostatic hypotension was defined using consensus definitions and persistent orthostatic hypotension was defined as 5 or more measurements with orthostatic hypotension. Difference in survival was analyzed 36 months after baseline.

Results

There was a high frequency of persistent orthostatic blood pressure (50%), constipation (30%) and incontinence (30%). Patients with persistent orthostatic hypotension had a significantly shorter survival compared to those with no or non-persistent orthostatic hypotension (Log rank x2 = 4.47, p = 0.034). Patients with constipation and/or urinary incontinence, in addition to persistent orthostatic hypotension, had a poorer prognosis compared to those with isolated persistent orthostatic hypotension or no orthostatic hypotension (Log rank x2 = 6.370, p = 0.041).

Discussion

According to our findings, the identification of autonomic dysfunction seems to be of great importance in clinical practice, not only to avoid falls and other complications, but also as a possible predictor of survival.

Background

Detecting cognitive impairment in medical inpatients is important due to its association with adverse outcomes. Our aim was to study recognition of cognitive impairment and its association with mortality.

Methods

200 inpatients aged over 60 years were recruited at the Department of General Internal Medicine at University Hospital MAS in Malmö, Sweden. The MMSE (Mini-Mental State Examination) and the CDT (Clock-Drawing Test) were performed and related to recognition rates by patients, staff physicians, nurses and informants. The impact of abnormal cognitive test results on mortality was studied using a multivariable Cox proportional hazards regression.

Results

55 patients (28%) had no cognitive impairment while 68 patients (34%) had 1 abnormal test result (on MMSE or CDT) and 77 patients (39%) had 2 abnormal test results. Recognition by healthcare professionals was 12% in the group with 1 abnormal test and 44-64% in the group with 2 abnormal test results. In our model, cognitive impairment predicted 12-month mortality with a hazard ratio (95% CI) of 2.86 (1.28-6.39) for the group with 1 abnormal cognitive test and 3.39 (1.54-7.45) for the group with 2 abnormal test results.

Conclusions

Cognitive impairment is frequent in medical inpatients and associated with increased mortality. Recognition rates of cognitive impairment need to be improved in hospitals.

Introduction

Early identification of Alzheimer’s disease (AD) is needed both for clinical trials and in clinical practice. In this study, we compared brief cognitive tests and cerebrospinal fluid (CSF) biomarkers in predicting conversion from mild cognitive impairment (MCI) to AD.

Methods

At a memory clinic, 133 patients with MCI were followed until development of dementia or until they had been stable over a mean period of 5.9 years (range 3.2–8.8 years). The Mini-Mental State Examination (MMSE), the clock drawing test, total tau, tau phosphorylated at Thr181 (P-tau) and amyloid-β1–42 (Aβ42) were assessed at baseline.

Results

During clinical follow-up, 47% remained cognitively stable and 53% developed dementia, with an incidence of 13.8%/year. In the group that developed dementia the prevalence of AD was 73.2%, vascular dementia 14.1%, dementia with Lewy bodies (DLB) 5.6%, progressive supranuclear palsy (PSP) 4.2%, semantic dementia 1.4% and dementia due to brain tumour 1.4%. When predicting subsequent development of AD among patients with MCI, the cognitive tests classified 81% of the cases correctly (AUC, 0.85; 95% CI, 0.77–0.90) and CSF biomarkers 83% (AUC, 0.89; 95% CI, 0.82–0.94). The combination of cognitive tests and CSF (AUC, 0.93; 95% CI 0.87 to 0.96) was significantly better than the cognitive tests (p = 0.01) and the CSF biomarkers (p = 0.04) alone when predicting AD.

Conclusions

The MMSE and the clock drawing test were as accurate as CSF biomarkers in predicting future development of AD in patients with MCI. Combining both instruments provided significantly greater accuracy than cognitive tests or CSF biomarkers alone in predicting AD.

We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPα sAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPα and sAPPβ levels between the groups. Significant correlations were observed between sAPPα and sAPPβ and between sAPPβ and Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPα and sAPPβ levels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPα correlated with p-Tau and sAPPβ with Aβ40. The differential association between sAPPα and sAPPβ with Aβ and Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.

Introduction

The objective of this study was to describe the longitudinal cognitive outcome in Alzheimer's disease (AD) and analyze factors that affect the outcome, including the impact of different cholinesterase inhibitors (ChEI).

Methods

In an open, three-year, nonrandomized, prospective, multicenter study, 843 patients were treated with donepezil, rivastigmine, or galantamine in a routine clinical setting. At baseline and every six months, patients were assessed using several rating scales, including the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the dose of ChEI was recorded. Sociodemographic and clinical characteristics were investigated. The relationships of these predictors with longitudinal cognitive ability were analyzed using mixed-effects models.

Results

Slower long-term cognitive decline was associated with a higher cognitive ability at baseline or a lower level of education. The improvement in cognitive response after six months of ChEI therapy and a more positive longitudinal outcome were related to a higher mean dose of ChEI, nonsteroidal anti-inflammatory drug (NSAID)/acetylsalicylic acid usage, male gender, older age, and absence of the apolipoprotein E (APOE) ε4 allele. More severe cognitive impairment at baseline also predicted an improved response to ChEI treatment after six months. The type of ChEI agent did not influence the short-term response or the long-term outcome.

Conclusions

In this three-year AD study performed in a routine clinical practice, the response to ChEI treatment and longitudinal cognitive outcome were better in males, older individuals, non-carriers of the APOE ε4 allele, patients treated with NSAIDs/acetylsalicylic acid, and those receiving a higher dose of ChEI, regardless of the drug agent.

Introduction

There is a great need for quick tests that identify treatment response in Alzheimer's disease (AD) to determine who benefits from the treatment. In this study, A Quick Test of cognitive speed (AQT) was compared with the mini-mental state examination (MMSE) in the evaluation of treatment outcome in AD.

Methods

75 patients with mild to moderate AD at a memory clinic were assessed with AQT and the MMSE at a pretreatment visit, at baseline and after 8 weeks of treatment with cholinesterase inhibitors (ChEI) initiated at baseline. Changes in the mean test scores before and after treatment were compared, as well as the number of treatment responders detected by each test, according to a reliable change index (RCI).

Results

After 8 weeks of treatment, the AQT improvement, expressed as a percentage, was significantly greater than that of the MMSE (P = 0.026). According to the RCI, the cut-offs to define a responder were ≥16 seconds improvement on AQT and ≥3 points on the MMSE after 8 weeks. With these cut-offs, both tests falsely classified ≤5% as responders during the pretreatment period. After 8 weeks of treatment, AQT detected significantly more responders than the MMSE (34% compared with 17%; P = 0.024). After 6 months of treatment, the 8-week AQT responders still showed a significantly better treatment response than the AQT nonresponders (22.3 seconds in mean difference; P < 0.001).

Conclusions

AQT detects twice as many treatment responders as the MMSE. It seems that AQT can, already after 8 weeks, identify the AD patients who will continue to benefit from ChEI treatment.

Background

The CSF biomarkers tau and Aβ42 can identify patients with AD, even during the preclinical stages. However, previous studies on longitudinal changes of tau and Aβ42 in individual patients with AD and elderly controls report somewhat inconsistent results.

Methodology/Principal Findings

We investigated the levels of tau and Aβ42 at baseline and after 1 year in 100 patients with AD. In a second cohort of 45 AD patients we measured the CSF biomarkers at baseline and after 2 years. Moreover, in 34 healthy elderly controls the CSF biomarkers were followed for 4 years. The baseline levels of tau were increased with >60% in AD patients compared to controls (p<0.001), while baseline Aβ42 levels were decreased with >50% (p<0.001). In the AD group followed for 2 years, tau increased with 16% compared to the baseline levels (p<0.05). However, the levels of tau were stable over 4 years in the controls. The levels of Aβ42 did not change significantly over time in any of the groups. In the patients with AD, tau was moderately associated with worse cognitive performance already at baseline (p<0.05).

Conclusions/Significance

Tau and Aβ42 in CSF seem to reflect the underlying disease state in both early and late stages of AD. The slight increase in tau over time observed in the patients with AD is modest when compared to the relatively large difference in absolute tau levels between AD patients and controls. Therefore, these markers maintain their usefulness as state markers over time and might serve as surrogate markers for treatment efficacy in clinical trials.

Most nuclear medicine clinicians use only visual assessment when interpreting regional cerebral blood flow (rCBF) from single-photon emission computed tomography (SPECT) images in clinical practice. The aims of this study were to develop a new, easy to use, automated method for quantification of rCBF-SPECT and to create normal values by using the method on a normal population. We developed a 3-dimensional method based on a brain-shaped model and the active-shape algorithm. The method defines the surface shape of the brain and then projects the maximum counts 0–1·5 cm deep for designated surface points. These surface projection values are divided into cortical regions representing the different lobes and presented relative to the whole cortex, cerebellum or cerebellar maximum. 99mTc-hexa methyl propylene amine oxime (HMPAO) SPECT was performed on 30 healthy volunteers with a mean age of 74 years (range 64–98). The ability of the active-shape algorithm to define the shape of the brain was satisfactory when visually scrutinized. The results of the quantification show rCBF values in the frontal, temporal and parietal lobes of 87–88% using cerebellum as the reference. There were no significant differences in normal rCBF values between male and female subjects and only a weak relation between rCBF and age. In conclusion, our new automated method was able to quantify rCBF-SPECT images and create normal values in ranges as expected. Further studies are needed to assess the clinical value of this method and the normal values.